Apoptosis means a process in which a certain cell leads to death as a result of programmed cell death in the development, differentiation, and maturation of cells or individuals, or as a result of cell death that is induced under various circumstances. It is considered that such apoptosis takes place under various physiological conditions. The morphological characteristics of apoptosis include absence of contact with surrounding cells, concentration of the cytoplasm, condensation of the chromatin or nucleus associated with the activity of endonuclease, segmentation of the nucleus, and the like. Regarding such apoptosis, disappearance of microvillus on the cell surface, smoothing of the cell surface (formation of bubbles on the cell surface; membranece blebbing), and the like are also observed. It has been reported that a phenomenon is also observed where DNA is fragmentized by endonuclease activity, and the final cell fragment as an apoptotic body has a mechanism whereby it is englobed by cells adjacent thereto [Immunology Today, 7 (4), 115-119 (1986)].
It has been clarified that apoptosis has an important relationship with various types of diseases. In recent years, various attempts have been made to diagnose, prevent, and treat such diseases by inducing or suppressing the apoptosis of cells.
Apoptosis is also call programmed cell death, and this term means a certain type of cell death occurring as a normal physiological process in many tissues. Apoptosis takes place as a result of activation of a genetic program provided in a cell itself. Finally, such apoptotic cells are removed by surrounding phagocytes without causing any inflammation (Shigekazu Nagata, (1998), Jikken Igaku (Experimental Medicine), Vol. 16, 1242-1246). It has been known that apoptosis is associated with not only a normal physiological process, but also with the onset of serious diseases such as cancer, autoimmune disease, or neurodegenerative disease. Thus, it is strongly desired that a method for inducing or inhibiting apoptosis so as to treat the aforementioned diseases, and an agent useful for such a method, will be developed. With regard to an apoptosis-inducing mechanism, the following facts have been clarified in detail to date. That is, apoptosis takes place as a result of a process of inducing apoptosis by a Fas antigen or a ligand of a tumor necrosis factor receptor that binds to its receptor located on the surface of an animal cell (Nagata, S., (1997) Cell, 88, 355-365), or as a result of activation of an intracellular pathway that induces apoptosis, due to cancer cells damaged by anticancer agents or X-ray irradiation (Haldar, S., et al., (1995) Proc. Natl. Acad. Sci. USA 92, 4507-4511).